CXA1_DANRE
ID CXA1_DANRE Reviewed; 381 AA.
AC O57474; Q5TYN6; Q7ZTS1;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Gap junction alpha-1 protein;
DE AltName: Full=Connexin-43;
DE Short=Cx43;
DE AltName: Full=Short fin protein;
GN Name=gja1; Synonyms=cx43, shf, sof;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, MUTAGENESIS OF PHE-30; PRO-191
RP AND PHE-209, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=C32;
RX PubMed=15649473; DOI=10.1016/j.ydbio.2004.11.005;
RA Iovine M.K., Higgins E.P., Hindes A., Coblitz B., Johnson S.L.;
RT "Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins.";
RL Dev. Biol. 278:208-219(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING (ISOFORMS 1
RP AND 2), DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=15895415; DOI=10.1002/dvdy.20426;
RA Chatterjee B., Chin A.J., Valdimarsson G., Finis C., Sonntag J.M.,
RA Choi B.Y., Tao L., Balasubramanian K., Bell C., Krufka A., Kozlowski D.J.,
RA Johnson R.G., Lo C.W.;
RT "Developmental regulation and expression of the zebrafish connexin43
RT gene.";
RL Dev. Dyn. 233:890-906(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=SJD;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14648847; DOI=10.1002/dvdy.10436;
RA Cheng S., Christie T., Valdimarsson G.;
RT "Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish
RT (Danio rerio) lens development.";
RL Dev. Dyn. 228:709-715(2003).
CC -!- FUNCTION: One gap junction consists of a cluster of closely packed
CC pairs of transmembrane channels, the connexons, through which materials
CC of low MW diffuse from one cell to a neighboring cell. Plays an
CC essential role in gap junction communication in the ventricles (By
CC similarity). {ECO:0000250|UniProtKB:P23242,
CC ECO:0000269|PubMed:15649473}.
CC -!- FUNCTION: Plays a role in regulation of fin bone size and growth.
CC {ECO:0000269|PubMed:15649473}.
CC -!- SUBUNIT: A connexon is composed of a hexamer of connexins. Interacts
CC with TMEM65. {ECO:0000250|UniProtKB:P23242}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P17302};
CC Multi-pass membrane protein {ECO:0000255}. Cell junction, gap junction
CC {ECO:0000250|UniProtKB:P17302}. Note=Localizes at the intercalated disk
CC (ICD) in cardiomyocytes and proper localization at ICD is dependent on
CC TMEM65. {ECO:0000250|UniProtKB:P23242}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O57474-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O57474-2; Sequence=VSP_015552;
CC Name=3;
CC IsoId=O57474-3; Sequence=VSP_015553;
CC -!- TISSUE SPECIFICITY: Expressed in adult ovary, heart, lens and liver. In
CC growing caudal fins, expressed in cells flanking the germinal region of
CC newly growing segments and in osteoblasts at segment boundaries.
CC {ECO:0000269|PubMed:14648847, ECO:0000269|PubMed:15649473,
CC ECO:0000269|PubMed:15895415}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Zygotic
CC expression is initiated before gastrulation and persists through to day
CC 5 of development. Levels increase in late somitogenesis, and late
CC embryonic and early larval stages. Embryonic expression is observed in
CC many developing tissues and organs, including the notochord and brain,
CC and heart and vasculature. Detected throughout the lens at 24 hours
CC post-fertilization (hpf), but by 3-4 days development, restricted to
CC the lateral epithelium and differentiating cells in the equatorial
CC region. {ECO:0000269|PubMed:14648847, ECO:0000269|PubMed:15895415}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC heart folding defects, reduced hematopoiesis and small eyes.
CC {ECO:0000269|PubMed:15649473}.
CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II)
CC subfamily. {ECO:0000305}.
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DR EMBL; AF035481; AAC04759.1; -; mRNA.
DR EMBL; AY313942; AAQ62128.1; -; Genomic_DNA.
DR EMBL; AY340236; AAQ17183.1; -; Genomic_DNA.
DR EMBL; CR352322; CAH69065.1; -; Genomic_DNA.
DR EMBL; CR352322; CAH69066.1; -; Genomic_DNA.
DR EMBL; BC049297; AAH49297.1; -; mRNA.
DR RefSeq; NP_571113.1; NM_131038.1. [O57474-1]
DR AlphaFoldDB; O57474; -.
DR SMR; O57474; -.
DR IntAct; O57474; 1.
DR MINT; O57474; -.
DR STRING; 7955.ENSDARP00000061260; -.
DR TCDB; 1.A.24.1.11; the gap junction-forming connexin (connexin) family.
DR PaxDb; O57474; -.
DR Ensembl; ENSDART00000061261; ENSDARP00000061260; ENSDARG00000041799. [O57474-1]
DR Ensembl; ENSDART00000138569; ENSDARP00000114698; ENSDARG00000041799. [O57474-3]
DR Ensembl; ENSDART00000181663; ENSDARP00000150086; ENSDARG00000041799. [O57474-3]
DR GeneID; 30236; -.
DR KEGG; dre:30236; -.
DR CTD; 30236; -.
DR ZFIN; ZDB-GENE-991105-4; gja1b.
DR eggNOG; ENOG502QRAE; Eukaryota.
DR GeneTree; ENSGT01050000244914; -.
DR HOGENOM; CLU_037388_0_0_1; -.
DR InParanoid; O57474; -.
DR OMA; LIQWYMY; -.
DR OrthoDB; 823525at2759; -.
DR PhylomeDB; O57474; -.
DR TreeFam; TF329606; -.
DR Reactome; R-DRE-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
DR Reactome; R-DRE-190861; Gap junction assembly.
DR Reactome; R-DRE-190873; Gap junction degradation.
DR Reactome; R-DRE-191650; Regulation of gap junction activity.
DR Reactome; R-DRE-196025; Formation of annular gap junctions.
DR Reactome; R-DRE-9013406; RHOQ GTPase cycle.
DR Reactome; R-DRE-9013409; RHOJ GTPase cycle.
DR PRO; PR:O57474; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000041799; Expressed in brain and 104 other tissues.
DR ExpressionAtlas; O57474; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005922; C:connexin complex; ISS:UniProtKB.
DR GO; GO:0005921; C:gap junction; IDA:ZFIN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ZFIN.
DR GO; GO:0005243; F:gap junction channel activity; IDA:ZFIN.
DR GO; GO:0055077; F:gap junction hemi-channel activity; IDA:ZFIN.
DR GO; GO:0022832; F:voltage-gated channel activity; IDA:ZFIN.
DR GO; GO:0098868; P:bone growth; IMP:ZFIN.
DR GO; GO:0060349; P:bone morphogenesis; IMP:ZFIN.
DR GO; GO:0035143; P:caudal fin morphogenesis; IMP:ZFIN.
DR GO; GO:0007154; P:cell communication; IDA:ZFIN.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IMP:ZFIN.
DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:ZFIN.
DR GO; GO:0035162; P:embryonic hemopoiesis; IMP:ZFIN.
DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IMP:ZFIN.
DR GO; GO:0033333; P:fin development; IMP:ZFIN.
DR GO; GO:0033334; P:fin morphogenesis; IGI:ZFIN.
DR GO; GO:0031101; P:fin regeneration; IMP:ZFIN.
DR GO; GO:0070121; P:Kupffer's vesicle development; IMP:ZFIN.
DR GO; GO:0033338; P:medial fin development; IMP:ZFIN.
DR GO; GO:0099111; P:microtubule-based transport; ISS:UniProtKB.
DR Gene3D; 1.20.1440.80; -; 1.
DR Gene3D; 1.20.5.1130; -; 1.
DR InterPro; IPR035091; Alpha_helix_dom_sf.
DR InterPro; IPR000500; Connexin.
DR InterPro; IPR002261; Connexin43.
DR InterPro; IPR013124; Connexin43_C.
DR InterPro; IPR034634; Connexin_C.
DR InterPro; IPR019570; Connexin_CCC.
DR InterPro; IPR017990; Connexin_CS.
DR InterPro; IPR013092; Connexin_N.
DR InterPro; IPR038359; Connexin_N_sf.
DR PANTHER; PTHR11984; PTHR11984; 1.
DR PANTHER; PTHR11984:SF33; PTHR11984:SF33; 1.
DR Pfam; PF00029; Connexin; 1.
DR Pfam; PF03508; Connexin43; 1.
DR PRINTS; PR00206; CONNEXIN.
DR PRINTS; PR01132; CONNEXINA1.
DR SMART; SM00037; CNX; 1.
DR SMART; SM01089; Connexin_CCC; 1.
DR SUPFAM; SSF118220; SSF118220; 1.
DR PROSITE; PS00407; CONNEXINS_1; 1.
DR PROSITE; PS00408; CONNEXINS_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; Gap junction; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT CHAIN 2..381
FT /note="Gap junction alpha-1 protein"
FT /id="PRO_0000057807"
FT TOPO_DOM 2..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..76
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..155
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..207
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT REGION 317..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 54..192
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT DISULFID 187..198
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_015552"
FT VAR_SEQ 13..52
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_015553"
FT MUTAGEN 30
FT /note="F->V: In shf(j7e1); short fin ray segments."
FT /evidence="ECO:0000269|PubMed:15649473"
FT MUTAGEN 191
FT /note="P->S: In shf(j7e2); short fin ray segments."
FT /evidence="ECO:0000269|PubMed:15649473"
FT MUTAGEN 209
FT /note="F->I: In shf(j7e3); short fin ray segments."
FT /evidence="ECO:0000269|PubMed:15649473"
FT CONFLICT 179
FT /note="F -> S (in Ref. 4; AAH49297)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="H -> R (in Ref. 4; AAH49297)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 381 AA; 43455 MW; 6120920232CA7527 CRC64;
MGDWSALGRL LDKVQAYSTA GGKVWLSVLF IFRILVLGTA VESAWGDEQS AFKCNTQQPG
CENVCYDKSF PISHVRFWVL QIIFVSTPTL LYLAHVFYLM RKEEKLNRKE EELKAVQNDG
GDVELHLKKI ELKKFKHGLE EHGKVKMKGS LLRTYIFSII FKSICEVVFL VIQWYLYGFS
LSAVYTCERT PCPHRVDCFL SRPTEKTIFI IFMLVVSLFS LLLNIIELFY VLFKRIKDRV
KSRQNTQFPT GTLSPTPKEL STTKYAYYNG CSSPTAPLSP MSPPGYKLAT GERTNSCRNY
NKQANEQNWA NYSTEQNRLG QNGSTISNSH AQAFDYPDDT HEHKKLTPGH ELQPLALIDA
RPCSRASSRM SSRARPDDLD V
